Identification of a particular genotype responsible for a given phenotype is an essential goal underlying gene-based medicine because it affords a rational departure point for the development of successful strategies for disease management, therapy and even cure. While, by one recent estimate, only two percent (2%) of the human genome has yet been sequenced, perhaps more than 50% of expressed human genes are at least partially represented in existing databases (Duboule, D., Oct. 24, 1997, Editorial: The Evolution Of Genomics, Science 278, 555). It is therefore quite clear that understanding functional interactions among the products of expressed genes represents the next great challenge in medicine and biology. This pursuit has been referred to as "functional genomics," although this term is perhaps too broad to have a clear meaning (Heiter, P. and Boguski, M., Oct. 24, 1997, Functional Genomics: It's All How You Read It, Science 278, 601-602). Nevertheless, it is the prevailing view that functional genomics generally describes " . . . a transition or expansion from the mapping and sequencing of genomes . . . to an emphasis on genome function." (Id.). Further, this new emphasis will require " . . . creative thinking in developing innovative technologies that make use of the vast resource of structural genomics information." Perhaps the best definition of functional genomics is " . . . the development and application of global (genome-wide or system-wide) experimental approaches to assess gene function by making use of the information provided by structural genomics." (Id., emphasis added).
One of the major advantages of the present invention is the circumvention of large-scale sequencing in determining functional relationships among genes. The VGID.SM. method of the present invention is a straightforward yet very powerful genetic comparison or subtraction technique. Functional information is obtained from global (i.e. genome-wide) expressed gene comparison of two or more user-defined phenotypes using mismatch binding protein chromatography. With the VGID.SM. method, disease genes may be identified over a time period of weeks, unlike the years required to succeed using positional cloning.